Interplay between brain oxygenation and the development of hypothermia in endotoxic shock.

There is evidence to suggest that the hypothermia observed in the most severe cases of systemic inflammation or sepsis is a regulated response with potential adaptive value, but the mechanisms involved are poorly understood. Here, we investigated the interplay between brain oxygenation (assessed by tissue PO2) and the development of hypothermia in unanesthetized rats challenged with a hypotension-inducing dose of bacterial lipopolysaccharide (LPS, 1 mg/kg i.v.). At an ambient temperature of 22 °C, oxygen consumption (V̇O2) began to fall only a few minutes after the LPS injection, and this suppression in metabolic rate preceded the decrease in core temperature. No reduction in brain PO2 was observed prior to the development of the hypometabolic, hypothermic response, ruling out the possibility that brain hypoxia served as a trigger for hypothermia in this model. Brain PO2 was even increased. Such an improvement in brain oxygenation could reflect either an increased O2 delivery or a decreased O2 consumption. The former explanation seems unlikely because blood flow (cardiac output) was being progressively decreased during the recording period. On the other hand, the decrease in V̇O2 usually preceded the rise in PO2, and an inverse correlation between V̇O2 and brain PO2 was consistently observed. These findings do not support the existence of a closed-loop feedback relationship between brain oxygenation and hypothermia in systemic inflammation. The data are consistent with a feedforward mechanism in which hypothermia is triggered (possibly by cryogenic inflammatory mediators) in anticipation of changes in brain oxygenation to prevent the development of tissue hypoxia.